MAPT and Alzheimer disease: We expect that multiple patient-derived cryo-EM αS fibril structures will be reported, as they have been for tau and Aβ, using material derived from human patients with Alzheimer's disease or related neuropathies.41–43 With such structures available, an essential question for drug design will be whether they accurately represent the conformation (or conformations assuming that varying polymorphs underlie differences in synucleinopathies, as seen for tau) adopted by fibrils in vivo.